rs3755486

Variant names:

• chr2-174767158-C-T
• rs3755486
• ENST00000442996.1:n.322-5591C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000442996.1(ENSG00000236449):​n.322-5591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,962 control chromosomes in the GnomAD database, including 11,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11745 hom., cov: 31)
• Consequence: ENSG00000236449 ENST00000442996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 4 publications found

Genes affected

ENSG00000236449 (HGNC:):

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

CHRNA1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 1A

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• myasthenic syndrome, congenital, 1B, fast-channel

  Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000442996.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000236449	ENST00000442996.1	TSL:1	n.322-5591C>T		intron	N/A
	CHRNA1	ENST00000636168.2	TSL:5	c.-446-7525G>A		intron	N/A	ENSP00000490338.2
	ENSG00000236449	ENST00000842845.1		n.326+37334C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54564 AN: 151846 Hom.: 11752 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54559 AN: 151962 Hom.: 11745 Cov.: 31 AF XY: 0.355 AC XY: 26393 AN XY: 74266

African (AFR) AF: 0.119 AC: 4916 AN: 41470

American (AMR) AF: 0.432 AC: 6600 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1845 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1157 AN: 5172

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4808

European-Finnish (FIN) AF: 0.477 AC: 5027 AN: 10532

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32408 AN: 67942

Other (OTH) AF: 0.405 AC: 853 AN: 2104

Alfa AF: 0.457 Hom.: 13618

Bravo AF: 0.348

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3755486; hg19: chr2-175631886;